In view of the importance of steroids as therapeutic agents, there has been considerable effort spent in developing improved processes for preparing various steroidal species.
One such development has centered on the dehydrogenation of steroidal .DELTA..sup.3,5 enol ethers with 2,3-dichloro-5,6-dicyanobenzoquinone and similar reagents. See for example, Pradham et al., "The Dehydrogenation of Steroidal .DELTA..sup.3,5 Enol Ethers with Dichlorodicyanobenzoquinone(DDQ)", J. Organ. Chem., 29, pp. 601-604(1964); Fried et al., Organic Reactions in Steroid Chemistry, Vol. 1, pp. 308-313(Van Nostrand Reinhold Company, New York, 1972); and Walker et al., "2,3-Dichloro-5,6-Dicyanobenzoquinone and Its Reactions", Chem. Rev., 67, pp. 153-195(1967).
Burn et al., Chemistry and Industry, p. 497(1966) reported the formation of 17-.alpha.-acetoxy-6-hydroxymethyl-3-methoxypregna-4,6-diene-20-one with 2,3-dichloro-5,6-dicyanobenzoquinone(DDQ) as the reagent in aqueous acetone and suggested extension of that reaction to other 3-alkoxy-6-hydroxymethyl-4,6-dien-3-ones in the androstane, 19-norandrostane, pregnane and corticoid species.
It has now been found that the yields can be improved and other advantages obtained by the electrochemical dehydrogenation of the .DELTA..sup.3,5 enol ethers with 2,3-dichloro-5,6-dicyanobenzoquinone, or another suitable high potential quinone, in a basic system. This process provides an unexpected increase in the yields obtained by the chemical dehydrogenations of the prior art, has the further advantage of providing end product of greater purity, is a cleaner reaction, is operable with catalytic or less than stoichiometric amounts of the quinone, and further allows for the regeneration and recovery of the catalyst when 2,3-dichloro-5,6-dicyanobenzoquinone or 2,3-dichloro-5,6-dicyanohydroquinone is employed. In both cases, DDQ is recovered. The results obtained are particularly surprising since the quinones are base sensitive.
The regeneration and recovery of 2,3-dichloro-5,6-dicyanobenzoquinone by the anodic oxidation of 2,3-dichloro-5,6-dicyanohydroquinone has been reported by Brinker et al. Synthesis, p. 671(1975). However, there has been no suggestion of using the quinones in electrochemical dehydrogenation of steroids. Other high potential quinones useful in the practice of the present invention are disclosed by Jackman, "Hydrogenation-Dehydrogenation Reactions", Advances in Organic Chemistry, Vol. 2, pp. 329-333(Interscience Publishers, Inc., New York,1960).